PROJECT SUMMARY/ABSTRACT Adolescence is a vulnerable developmental stage where significant changes occur in a youth?s central nervous system. Pharmacological stressors, such as drugs of abuse, can have a profound impact on these changes during adolescence. Marijuana (MJ), second to alcohol, is the most widely used intoxicant in adolescents. A staggering 36% high-school seniors reported using MJ in the past year and 21% in the past month. Of course, many adolescents who experiment with MJ only do so during adolescence and experience little to no long-term effects. Nonetheless, a significant minority does experience problems and their initial MJ experimentation can escalate to extremely adverse outcomes including addiction and other psychiatric conditions. However, the precise neurobiological underpinnings of such transition is not well-understood, but are posited to be associated with reward dysfunction. During the K01 award period, the Candidate will pursue an innovative line of research examining the impact of initial MJ use on reward processing in adolescent MJ users, while also receiving essential training required to conduct such research. Specifically, the project will examine neural mechanisms underpinning reward dysfunction in adolescent MJ users via multimodal neuroimaging [electroencephalography (EEG) and a functional magnetic resonance imaging (fMRI)], and test whether these neuroimaging markers predict escalation of disease symptomology at 12-month follow-up. Embedded within this novel project are clear training aims, which will be implemented with guidance from a multidisciplinary mentoring team of renowned research scientists. The proposed training plan will develop competency in (1) clinical characterization of adolescent substance use; (2) utilization of fMRI to study reward circuity; and (3) advance biostatistics for clinical outcome assessment. At baseline, MJ-using adolescents and MJ-nave control adolescents will perform tasks that probe reward anticipation and attainment stages of reward processing, separately with EEG and fMRI. Participants will also undergo a resting-state fMRI scan for precise delineation of the neuronal circuitry underlying reward processing. Lastly, participants will return 12 months after baseline for a clinical follow-up. The goal is to investigate whether baseline neuroimaging markers of reward dysfunction predict escalation in substance use symptomatology. Importantly, Icahn School of Medicine at Mount Sinai is an ideal environment to conduct neuroimaging research with children and adolescents, as it boasts fully-equipped Pediatric Mood and Anxiety Disorders Program (P-MAP; Chief: Dr. Gabbay) to conduct interviews and behavioral testing, and the Brain Imaging Center (BIC; Chief: Dr. Goldstein) for EEG and fMRI scanning. Collectively, the proposed research and training goals will provide the Candidate with a strong foundation in adolescent psychopathological assessment and functional neuroimaging, facilitate in launching his independent research career, while also significantly advancing our understanding of neurocognitive mechanisms underlying adolescent substance use.